Are you sure your patient has transposition of the great vessels? What are the typical findings for this disease?

Transposition of the great vessels, also called TGV, typically presents in the neonatal period. It is sometimes also called transposition of the great arteries, or TGA. Often it is diagnosed during a prenatal ultrasound. However, if it is not, it typically has the following presentation:

TGV commonly presents with cyanosis. There can be a reverse saturation gradient, with more severe cyanosis in the upper body (above the ductus arteriosus) than in the lower body (below the ductus arteriosus).

TGV can present with shortness of breath.

If not diagnosed before discharge from the newborn nursery, TGV can present in the first weeks of life with poor appetite and poor weight gain.

The anatomy of TGV leads to parallel pathways of circulation. Figure 1 shows that in "transposition circulation," desaturated blood from systemic veins drains to the right atrium, then to the right ventricle, and then to the aorta, where desaturated blood returns to the systemic circulation. Saturated blood from the pulmonary veins drains to the left atrium, then to the left ventricle, then to the pulmonary artery, where saturated blood returns to the pulmonary circulation.

Figure 1.

Systemic and pulmonary circulation run in parallel in transposition, whereas in normal circulation they run in series.

What other disease/condition shares some of these symptoms?

1) Tetralogy of Fallot

2) Pulmonary atresia

3) Ebstein's anomaly of the tricuspid valve

4) Tricuspid atresia

5) Total anomalous pulmonary venous return

What caused this disease to develop at this time?

Transposition is a congenital heart defect; that is, it occurs during cardiac development in utero. Development of the infundibulum of the heart (conus) results in normal great vessel orientation between days 30 and 34 of gestation; abnormalities in this development can lead to TGV.

The etiology of TGV is typically unknown; however, it has been associated with maternal diabetes and exposure to retinoic acid.

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

Since TGV often presents shortly after birth with cyanosis, the first study typically performed is a spot check oxygen saturation with a pulse oximeter. Saturations in TGV are typically in the 80's or lower, and with a patent ductus arteriosus saturation are typically higher in the lower extremities compared with the upper extremities (reverse saturation gradient).

If cyanosis is confirmed by pulse oximetry, an urgent echocardiogram should be the next study ordered.

Would imaging studies be helpful? If so, which ones?

Echocardiogram is the definitive study used to diagnose TGV and distinguish it from other congenital heart defects. This test should be performed by a sonographer or physician with experience in imaging congenital heart defects, and should be interpreted by a pediatric cardiologist. Great care should be made to determine the complete cardiac anatomy of the patient, as there is considerable variation in the associated defects seen with TGV, all of which are important factors in deciding on the proper treatment strategy.

Anatomic variables in transposition of the great vessels

Coronary anatomy - Coronaries arise from the native aorta (connected to the right ventricle). They can arise from the usual sinuses (70%), or from a variety of orientations, including left circumflex from right, single left, single right, or intramural course of either coronary. Coronary anatomy can affect surgical approach to repair, as repair for TGV typically includes transfer of coronary arteries from one great vessel to another.

Atrial septum - Atrial septal defect (ASD) is important in allowing for mixing of blood between the systemic and pulmonary circulations. If the ASD is too small, a balloon septostomy may be urgently required. This is a temporizing procedure which may stabilize an infant prior to definitive surgical repair.

Patent ductus arteriosus - PDA is often needed to allow for adequate mixing of blood between the systemic and pulmonary circulations. Prostaglandins may be required to maintain ductal patency.

Outflow tracts and semilunar valve anatomy - Obstruction to either outflow tract or discrepancy between sizes of aortic and pulmonary valves can affect ability to surgically repair TGV.

Confirming the diagnosis

There is no clinical decision algorithm per se for evaluating for TGV, although typically a patient will present with cyanosis soon after birth; an echocardiogram is then indicated to determine the presence or absence of congenital heart disease. An echocardiogram is the standard accepted method of diagnosing TGV.

If you are able to confirm that the patient has transposition of the great vessels, what treatment should be initiated?

There are two therapies typically considered immediately after diagnosis: infusion of prostaglandin E1 (PGE1) and balloon atrial septostomy. Both of these will depend on the degree of cyanosis and the amount of mixing seen at the atrial septum on echocardiogram. For patients with significant cyanosis (typically oxygen saturations <85%), PGE1 infusion should be initiated immediately. If the child will need transfer to another institution for surgical correction, PGE1 should be started prior to transfer if possible, via central venous line. This allows for maintenance of patency of the ductus arteriosus, which promotes more mixing of blood between the pulmonary and systemic circulations.

The decision of whether to perform balloon atrial septostomy depends on a host of factors. One is the length of time anticipated before surgical repair. Another is the degree of cyanosis of the patient. Another is the estimated size of the atrial septal defect based on the echocardiogram. While septostomy used to be a routine part of initial treatment for patients with TGV, this practice is now being re-examined because definitive surgical repair is being undertaken in the first week of life in most cases, obviating the need for the septostomy. If a septostomy is indicated, it should be performed by a pediatric cardiologist with experience in the procedure, either in a cardiac catheterization laboratory or at the bedside under echo guidance. Most commonly, the catheter is introduced via the umbilical vein.

Definitive treatment for TGV is surgical. While prior surgical approaches included creation of baffles in the atria to direct systemic venous return to the pulmonary artery and pulmonary venous return to the aorta (Mustard or Senning operations), in the modern era the most commonly performed operation is the arterial switch operation (ASO). This involves disconnecting the ascending aorta and pulmonary artery from their roots, switching the vessels to the other valve (called the LeCompte maneuver), and re-attaching the vessels to their new roots. Additionally, the coronary arteries must be switched from the native aorta (which arose from the right ventricle) to the native pulmonary artery (which arose from the left ventricle). After ASO, the valves are known as the neo-aortic and neo-pulmonary valves. This operation requires lengthy cardiopulmonary bypass.

If other associated lesions are present (such as atrial or ventricular septal defects), they are typically repaired at the time of ASO. Surgical considerations when there are valve size discrepancies or outflow tract obstruction are beyond the scope of this chapter, but typically require more complex repair, occasionally in multiple stages.

What are the adverse effects associated with each treatment option?

The adverse effects of PGE1 infusion are important to anticipate, recognize, and treat immediately. The most common adverse effect is apnea. Any time PGE1 is infused, bag-mask ventilation and preferably endotracheal ventilation should be readily available for immediate treatment. Lowering the dose of PGE1 can often resolve apnea. Other adverse effects include fever, vasodilation, and rash.

The adverse effects of balloon atrial septostomy are related primarily to the procedure itself. Although extremely rare in experienced hands, there have been reports of fatality due to tearing the atrial septum away from the inferior vena cava, resulting in immediate exsanguination. Other adverse effects are bleeding at the skin site where the catheter is introduced (umbilicus or femoral vein), pericardial effusion (from small tear in outside wall of atrium), stroke (from introduction of thrombus or air embolus to the systemic arterial system), or failure of the procedure to create an adequate atrial septal defect.

The adverse effects of the arterial switch operation (ASO) can be categorized into those related to any cardiac surgery and those specific to the ASO itself. All cardiac surgeries can be complicated by bleeding, infection, stroke, ventricular failure, and feeding difficulty after surgery (particularly in neonates).

Specific to the ASO, patients can have regurgitation of either the neo-aortic or neo-pulmonary valves, stenosis of the coronary ostia at the site of reimplantation, or (most commonly) stenosis of the pulmonary artery branches at the point of bifurcation. This can be treated in the future with balloon pulmonary arterioplasty and/or stent placement in the cardiac catheterization laboratory, or more rarely will require re-operation to improve the caliber of the pulmonary artery branches.

What are the possible outcomes of transposition of the great vessels?

Prognosis for TGV: The prognosis for patients born with TGV has improved dramatically over the last several decades, due to the advent of the balloon atrial septostomy, the routine infusion of PGE1 upon diagnosis, and significant improvements in cardiac surgery and post-operative management in the intensive care unit. The 5-year survival for straightforward TGV without other anatomic abnormalities is >95% in most centers. However, there is a somewhat higher occurrence of post-surgical morbidity, typically related to branch pulmonary artery stenosis after the LeCompte maneuver.

Families of patients born with TGV should be counseled that there are no alternatives to surgical correction other than comfort care, which, in today's era of good post-surgical survival, is not routinely recommended in developed countries. Most centers will perform surgical repair within the first week of life. The anticipated length of hospital stay after surgical repair with ASO ranges from 2-4 weeks, dependent primarily on the progress a child makes with feeding after surgery. Sternal healing takes 6 weeks.

What causes this disease and how frequent is it?

The incidence of TGV is 5%-7% of congenital heart defects, or approximately 5 in 10,000 live births. There is a 60%-70% male preponderance. There is no known seasonal variation. TGV is a congenital heart defect that is always present (and usually detected) at birth. There are no major environmental exposures that causes the development of TGV in the fetus, although maternal use of retinoic acid may be associated with development of TGV.

TGV is generally thought to be a sporadic congenital heart defect, although there are new insights into the pathogenesis of the disease being worked out, and in some reports a slightly higher risk of multiple family members having TGV exists compared with the normal incidence in the general population.

Other clinical manifestations that might help with diagnosis and management

One clue helpful in leading to the diagnosis of TGV (prior to performance of an echocardiogram) is a reverse differential in pre-ductal and post-ductal oxygen saturations, where arm saturations are lower than leg saturations. This is due to desaturated blood from the systemic veins coursing through the aorta and out to the arms, whereas fully saturated blood from the pulmonary veins courses through the pulmonary artery and then right to left across the patent ductus arteriosus into the lower extremities. Saturations that are higher in the legs than in the arms should be considered highly suspicious for TGV.

What complications might you expect from the disease or treatment of the disease?

Complications from treatment of TGV are typically related to the resultant anatomy of the heart and great vessels after ASO.

The most common complication is branch pulmonary artery stenosis at the bifurcation point. This is a result of stretch placed on the main neo-pulmonary artery after the LeCompte maneuver. The stretching places tension on the suture line, which can affect growth of the pulmonary artery. While a mild degree of stenosis is often well-tolerated and just needs to be followed by longitudinal echocardiograms, significant stenosis will require intervention. This can typically be performed in the cardiac catheterization laboratory through balloon arterioplasty with or without stent placement.

Another more serious, although fortunately less common, complication from treatment of TGV is stenosis of the coronary arteries related to reimplantation during surgery. Acutely, this can lead to myocardial ischemia and/or infarction in the immediate post-surgical period, with resultant poor ventricular function. Longer-term, stenosis can lead to chest pain and low myocardial function, as well as likely increased risk for myocardial infarction later in life.

Another complication from treatment of TGV is regurgitation from either the neo-aortic or neo-pulmonary valve. This can result from either direct damage to the leaflets from surgery or from disturbance of the normal geometry of the valve annulus from the LeCompte maneuver. While neo-pulmonary regurgitation is typically better tolerated than neo-aortic regurgitation, either can result in dilation of the adjacent ventricle and the need for valve replacement.

Are additional laboratory studies available; even some that are not widely available?

Sometimes echocardiography cannot determine coronary artery arrangement, in which case other imaging studies may be warranted prior to surgical repair to plan for the best approach. Many centers will perform cardiac catheterization with angiography of the coronary arteries, although increasingly cardiac MRI is taking the place of cardiac catheterization for anatomical inquiries such as this.

How can transposition of the great vessels be prevented?

Currently there is no way to prevent transposition of the great vessels.

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